Gene polymorphism of the renin-angiotensin system and progression of diabetic nephropathy

Good evidence exists that genetic predisposition is a major determinant in the development of renal and cardiovascular complications of diabetes. In particular, the role of familial predisposition is well established in diabetic nephropathy which may cluster within families, both in type I (IDDM) and in type II (NIDDM) diabetes. The genes responsible for predisposition to renal and cardiovascular complications are not known, but those of the renin-angiotensin system (RAS) are plausible candidates. Beside the large number of studies aimed at evaluating the role of polymorphisms in these genes, particularly in angiotensin-converting enzyme (ACE) gene, in development of renal disease, no clear-cut evidence has been provided until now. Furthermore, a number of trials have shown that ACE-inhibitors (ACEi) may reduce the rate of progression of renal failure. If the RAS genotype were able to foresee the response to ACEi it would provide new strategies for a specific treatment of subjects at higher risk.